title: Efficient network-guided multi-locus association mapping with graph cuts.
abstract: BACKGROUND
  As an increasing number of genome-wide association studies reveal the limitations of the attempt to explain phenotypic heritability by single genetic loci, there is a recent focus on associating complex phenotypes with sets of genetic loci. Although several methods for multi-locus mapping have been proposed, it is often unclear how to relate the detected loci to the growing knowledge about gene pathways and networks. The few methods that take biological pathways or networks into account are either restricted to investigating a limited number of predetermined sets of loci or do not scale to genome-wide settings.
  
  
  RESULTS
  We present SConES, a new efficient method to discover sets of genetic loci that are maximally associated with a phenotype while being connected in an underlying network. Our approach is based on a minimum cut reformulation of the problem of selecting features under sparsity and connectivity constraints, which can be solved exactly and rapidly. SConES outperforms state-of-the-art competitors in terms of runtime, scales to hundreds of thousands of genetic loci and exhibits higher power in detecting causal SNPs in simulation studies than other methods. On flowering time phenotypes and genotypes from Arabidopsis thaliana, SConES detects loci that enable accurate phenotype prediction and that are supported by the literature.
  
  
  BACKGROUND
  Code is available at http://webdav.tuebingen.mpg.de/u/karsten/Forschung/scones/.
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Machine Learning and Computational Biology Research Group, Max Planck Institute for Developmental Biology & Max Planck Institute for Intelligent Systems Spemannstr 38, 72076 Tübingen, Germany. chloe-agathe.azencott@tuebingen.mpg.de
authors.forename: Chloé-Agathe
authors.initials: CA
authors.lastname: Azencott
authors.forename: Dominik
authors.initials: D
authors.lastname: Grimm
authors.forename: Mahito
authors.initials: M
authors.lastname: Sugiyama
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kawahara
authors.forename: Karsten M
authors.initials: KM
authors.lastname: Borgwardt
mesh_terms: D017360:Arabidopsis / Q000235:genetics / Q000254:growth & development; D035264:Flowers; D056426:Genetic Loci; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006801:Humans; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide